1. Field of the Invention
The present invention relates to anthracyclinone glycoside antibiotics and processes for the preparation thereof. More particularly, the invention relates to the novel antibiotics, 4'-epi-6'-hydroxydaunomycin and 4'-epi-6'-hydroxyadriamycin. The invention also relates to certain novel intermediates used in the preparation of these antibiotics.
2. The Prior Art
Glycoside antibiotics are, of course, known. For example, daunomycin and its aglycone, daunomycinone are known compounds. They are described and claimed in British Pat. No. 1,003,383. Adriamycin and its aglycone, adriamycinone are also known compounds, being described and claimed in British Pat. No. 1,161,278; both such British patents being owned by the assignee hereof.
The above glycoside antibiotics are prepared according to the processes disclosed in application Ser. Nos. 560,104 and 560,105, incorporated herein by reference, by reacting the aglycone, or a reactive derivative thereof with a reactive protected derivative of the pyranose sugars daunosamine and 4'-epidaunosamine.
Application Ser. No. 568,437 describes a process for producing derivatives of daunomycin and adriamycin, which process utilizes a novel, reactive, protected derivative of a 1,2-unsaturated pyranoid sugar. These pyranoid sugars are known generically as "glycals". See, for example, the monograph entitled "Unsaturated Sugar, Advance in Carbohydrate Chemistry", Vol. 20, page 67 (1965, Academic Press, London). In this monograph a number of glycals including D-arabinal (3,4-di-O-acetyl); 0-acetyl); L-arabinal (3,4-di-O-acetyl); D-allal (4,6-O-benylidene); D-glucal (4-deoxy); L-glucal (3,4(-di-O-acetyl), etc., are described.
The process of the present invention also utilizes a novel, reactive, protected derivative of a 1,2-unsaturated pyranoid sugar, the latter being obtained from L-glucose according to techniques which are described in part in the literature, see, e.g. G. N. Bollenback; Methods in Carbohydrate Chemistry II, 326, 1963; L. F. Wiggins; ibid, II, 188, 1963 and A. C. Richardson; Carbohydrate Research, 4, 422, (1967).